Preservation of biopharmaceutical materials, such as a bulk drug substance (BDS), is important in the manufacture, use, transport, storage and sale of such materials. For example, bulk drug substance is often preserved by freezing during storage. Similarly, bulk drug substance is often frozen and thawed as part of the development process to enhance the quality or to simplify the development process. Bulk drug substance may also need to be stored and shipped at a certain temperature range.
When freezing bulk drug substance, the overall quality, and in particular pharmaceutical activity, of the bulk drug substance is desirably preserved, without substantial degradation of the bulk drug substance. When freezing or thawing an aqueous solution, such as bulk drug substance, temperature sensors (e.g., an RTD in a thermowell) have typically been used to monitor the process. Such a temperature sensor provides useful information at the beginning and end of a freeze or thaw as the solution loses or gains sensible heat. However, the sensor is of little use during the middle of a freeze or thaw, for about half of the process, because the loss or gain of latent heat due to phase change has no accompanying change in temperature. Unless an array of temperature sensors is used, there is no way to know to what extent the material has been frozen or thawed. Thus, it would be advantageous to have a sensor that can determine the extent of phase change in a material being frozen or thawed.
Thus, there is a need for systems and methods for freezing, thawing, and storing biopharmaceutical materials, which allow the monitoring of phase changes in such biopharmaceutical materials during freezing and thawing.